Vitamin C supplementation ameliorates the adverse effects of nicotine on placental hemodynamics and histology in nonhuman primates

Lo, Jamie O.; Schabel, Matthias C.; Roberts, Victoria H. J.; Morgan, Terry K.; Räsänen, Juha; Kroenke, Christopher D.; Shoemaker, Sophie R.; Spindel, Eliot R.; Frias, Antonio E.

doi:10.1016/j.ajog.2014.12.042

Cited by 26 publications

(22 citation statements)

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“…Maternal uterine artery blood flow (cQuta) and placental blood flow (cQuv) were calculated from Doppler ultrasound measurements of vessel diameter and velocity time integral as previously described. 1,26,27 There was no difference in cQuta either across gestation (G85 to G135) or between the 2 diet cohorts ( Figure 3C and D). We demonstrate a gestational agedependent increase in cQuv but no significant difference between the CON and PR cohorts ( Figure 3E and F).…”

Section: Uteroplacental Blood Flowmentioning

confidence: 92%

Adverse Placental Perfusion and Pregnancy Outcomes in a New Nonhuman Primate Model of Gestational Protein Restriction

Roberts

Lewandowski

et al. 2018

Reprod. Sci.

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Maternal malnutrition during pregnancy impacts fetal growth, with developmental consequences that extend to later life outcomes. In underdeveloped countries, this malnutrition typically takes the form of poor dietary protein content and quality, even if adequate calories are consumed. Here, we report the establishment of a nonhuman primate model of gestational protein restriction (PR) in order to understand how placental function and pregnancy outcomes are affected by protein deficiency. Rhesus macaques were assigned to either a control diet containing 26% protein or switched to a 13% PR diet prior to conception and maintained on this PR diet throughout pregnancy. Standard fetal biometry, Doppler ultrasound of uteroplacental blood flow, ultrasound-guided amniocentesis, and contrast-enhanced ultrasound (CE-US) to assess placental perfusion were performed mid-gestation (gestational day 85 [G85] where term is G168) and in the early third trimester (G135). Our data demonstrate that a 50% reduction in dietary protein throughout gestation results in reduced placental perfusion, fetal growth restriction, and a 50% rate of pregnancy loss. In addition, we demonstrate reduced total protein content and evidence of fetal hypoxia in the amniotic fluid. This report highlights the use of CE-US for in vivo assessment of placental vascular function. The ability to detect placental dysfunction, and thus a compromised pregnancy, early in gestation, may facilitate the development of interventional strategies to optimize clinical care and improve long-term offspring outcomes, which are future areas of study in this new model.

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Section: Uteroplacental Blood Flowmentioning

confidence: 92%

Adverse Placental Perfusion and Pregnancy Outcomes in a New Nonhuman Primate Model of Gestational Protein Restriction

Roberts

Lewandowski

et al. 2018

Reprod. Sci.

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“…Interestingly, at G135, fetal and placental outcomes are less severe. While the mechanism for this discrepancy is unknown, it is consistent with placental adaptive capabilities to transient environmental perturbations as has been observed in early acute injury to macaque placentas 46 when compared with chronic environmental perturbations throughout pregnancy 24,47 . Although the placental weight in ethanol exposed pregnancies compared to controls is less at G110, at G135 the placental weight was similar between both groups suggesting that the placenta partly compensates by altering its growth trajectory to support fetal growth, albeit that fetal weights are not fully restored to control weights.…”

Section: Commentmentioning

confidence: 57%

28: First trimester alcohol exposure alters placental perfusion and fetal oxygen availability affecting fetal growth and development in a non-human primate model

Schabel

Wang

et al. 2017

American Journal of Obstetrics and Gynecology

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Objective-Prenatal alcohol exposure leads to impaired fetal growth, brain development, and stillbirth. Placental impairment likely contributes to these adverse outcomes, but the mechanisms and specific vasoactive effects of alcohol linking altered placental function to impaired fetal development remain areas of active research. Recently, we developed MRI techniques in nonhuman primates to characterize placental blood oxygenation through measurements of T 2 *, and perfusion using dynamic contrast-enhanced (DCE) MRI. The objective of this study was to evaluate the effects of first trimester alcohol exposure on macaque placental function and to characterize fetal brain development, in vivo.Study Design-Timed-pregnant Rhesus macaques (n=12) were divided into 2 groups: control (n=6) and ethanol exposed (n=6). Animals were trained to orally self-administer either 1.5g/kg/day of a 4% ethanol solution (equivalent to 6 drinks/day) or an isocaloric control fluid from pre-conception until gestational day 60 (G60, term is G168). All underwent Doppler ultrasound (D-US) followed by MRI consisting of T 2 * and DCE measurements. D-US was used to measure uterine artery (Uta) and umbilical vein velocimetry and diameter to calculate Uta volume Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.The authors report no conflicts of interest.Presented orally at the 37 th Society of Maternal Fetal Medicine Annual Meetings in Las Vegas, Nevada, January 23-28 th , 2017Reprints will not be available. HHS Public Access Author Manuscript Author Manuscript Author ManuscriptAuthor Manuscript blood flow (cQuta) and placental volume blood flow (cQuv). After non-invasive imaging, animals underwent C-section delivery for placenta collection and fetal necropsy at G110 (n=6) or G135 (n=6).Results-Fetal weight and biparietal diameter were significantly smaller in ethanol exposed compared to controls at G110. By D-US, cQuta was decreased (p=0.1) and cQuv was significantly lower (p=0.04) at both G110 and G135 in ethanol exposed versus control animals. A significant reduction in placental blood flow was evident by DCE-MRI. As we demonstrated recently, T 2 * values vary throughout the placenta, and reveal gradients in blood deoxyhemoglobin concentration ranging from highly oxygenated blood (long T 2 *) proximal to spiral arteries to highly deoxygenated blood (short T 2 *). Distributions of T 2 * throughout the placenta show significant global reduction in T 2 * (and hence high blood deoxyhemoglobin concentration) in ethanol exposed vs. control at G110 (p=0.02). Fetal brain measurements indicated impaired grow...

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“…91 Using the Rhesus macaque model of nicotine exposure in pregnancy, 66,92,93 Vitamin C supplementation has been studied to determine if this potent antioxidant could counteract the oxidative damage from nicotine. 94 Soluble VEGF receptor-1 (sFlt-1) is a peptide secreted by the placenta and has been implicated in the etiology of preeclampsia. 95 Therefore, an understanding of how nicotine may alter proper sFlt-1 expression is important for pregnancy health.…”

Section: Placental Nachrsmentioning

confidence: 99%

The impact of tobacco chemicals and nicotine on placental development

Suter

Aagaard

2020

Prenatal Diagnosis

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Despite decades of messages warning about the dangers of tobacco use in pregnancy, 10% to 15% of pregnant women continue to smoke. Furthermore, an increased popularity of electronic nicotine delivery systems (ENDS) over the past decade in women of childbearing age raises parallel concerns regarding the effects of vaporized nicotine use in pregnancy. While research using animal models which mimic tobacco smoke and nicotine exposure in pregnancy have largely replicated findings in humans, few studies focus directly on the effects of these exposures on the placenta. Because the placenta is a fetal derived tissue, and nicotine and other components of tobacco smoke are either processed by or transported directly through the placenta, such studies help us understand the risks of these exposures on the developing fetus. In this review, we summarize research on the placenta and placental‐derived cells examining either tobacco smoke or nicotine exposure, including both histologic and subcellular (ie, epigenetic and molecular) modifications. Collectively, these studies reveal that tobacco and nicotine exposure are accompanied by some common and several unique molecular and epigenomic placental modifications. Consideration of the nature and sequelae of these molecular mediators of risk may help to better inform the public and more effectively curtail modifiable behavior.

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Vitamin C supplementation ameliorates the adverse effects of nicotine on placental hemodynamics and histology in nonhuman primates

Cited by 26 publications

References 54 publications

Adverse Placental Perfusion and Pregnancy Outcomes in a New Nonhuman Primate Model of Gestational Protein Restriction

Adverse Placental Perfusion and Pregnancy Outcomes in a New Nonhuman Primate Model of Gestational Protein Restriction

28: First trimester alcohol exposure alters placental perfusion and fetal oxygen availability affecting fetal growth and development in a non-human primate model

The impact of tobacco chemicals and nicotine on placental development

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